Constant-severe pain in chronic pancreatitis is associated with genetic loci for major depression in the NAPS2 cohort

被引：26

作者：

Dunbar, Ellyn ^{[1
,2
]}

Greer, Phil J. ^{[1
]}

Melhem, Nadine ^{[3
]}

Alkaade, Samer ^{[4
,17
]}

Amann, Stephen T. ^{[5
]}

Brand, Randall ^{[1
]}

Cote, Gregory A. ^{[6
,12
]}

Forsmark, Christopher E. ^{[7
]}

Gardner, Timothy B. ^{[8
]}

Gelrud, Andres ^{[1
,9
,18
]}

Guda, Nalini M. ^{[10
]}

LaRusch, Jessica ^{[1
,19
]}

Lewis, Michele D. ^{[11
]}

Machicado, Jorge D. ^{[1
,20
]}

Muniraj, Thiruvengadam ^{[1
,21
]}

Papachristou, Georgios, I ^{[1
,22
]}

Romagnuolo, Joseph ^{[12
,23
]}

Sandhu, Bimaljit S. ^{[13
,24
]}

Sherman, Stuart ^{[6
]}

Wilcox, Charles M. ^{[14
]}

Singh, Vikesh K. ^{[15
]}

Yadav, Dhiraj ^{[1
]}

Whitcomb, David C. ^{[1
,2
,16
]}

机构：

[1] Univ Pittsburgh, Dept Med, Room 401-4,3708 Fifth Ave, Pittsburgh, PA 15213 USA

[2] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA

[3] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA

[4] St Louis Univ, Dept Med, St Louis, MO 63103 USA

[5] North Mississippi Med Ctr, Tupelo, MS USA

[6] Indiana Univ Sch Med, Indianapolis, IN 46202 USA

[7] Univ Florida, Coll Med, Dept Med, Gainesville, FL USA

[8] Dartmouth Hitchcock Med Ctr, Sect Gastroenterol & Hepatol, Lebanon, NH 03766 USA

[9] Univ Cincinnati, Dept Med, Cincinnati, OH USA

[10] GI Associates, Milwaukee, WI USA

[11] Mayo Clin, Div Gastroenterol & Hepatol, Dept Med, Jacksonville, FL 32224 USA

[12] Med Univ South Carolina, Dept Med, Charleston, SC 29425 USA

[13] Virginia Commonwealth Univ Med Coll Virginia, Dept Med, Richmond, VA USA

[14] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA

[15] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA

[16] Univ Pittsburgh, Dept Cell Biol & Mol Physiol, Pittsburgh, PA 15213 USA

[17] Mercy Clin Gastroenterol, St Louis, MO USA

[18] GastroHealth, Miami, FL USA

[19] Ariel Precis Med, Pittsburgh, PA USA

[20] Mayo Clin Hlth Syst, Div Gastroenterol & Hepatol, Eau Claire, WI USA

[21] Yale Univ, Dept Med, Med Ctr, New Haven, CT 06520 USA

[22] Ohio State Univ, Dept Med, Columbus, OH 43210 USA

[23] Ralph H Johnson VAMC, Charleston, SC USA

[24] St Marys Hosp, Richmond, VA USA

来源：

JOURNAL OF GASTROENTEROLOGY | 2020年 / 55卷 / 10期

基金：

美国国家卫生研究院;

关键词：

Pain chronic; Chronic pancreatitis; Depression; Antidepressants; Human genetics; QUALITY-OF-LIFE; DIABETES-MELLITUS; CLINICAL PROFILE; RECURRENT ACUTE; RISK-FACTORS; DISORDERS; COMPONENT; VARIANTS; ETIOLOGY; INSIGHTS;

D O I：

10.1007/s00535-020-01703-w

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. Study A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity asconstant-severe pain(n = 787) versusnot constant-severe pain(n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. Results Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS,p < 2.2 x 10(- 16)). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). Conclusion Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted.

引用

页码：1000 / 1009

页数：10

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